C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1117
Nutritional rickets is treated with a balanced diet
sufficient in calcium, phosphorus, and vitamin D.
Exposure to sunlight also is important, especially for
premature infants and those on artificial milk feedings.
Supplemental vitamin D in excess of normal require-
ments is given for several months. Children with vita-
min D–dependent rickets caused by lack of the enzyme
needed to convert vitamin D to its active form are treated
with calcitriol, the active form of vitamin D.
29
Vitamin
D–resistant forms of rickets are treated with oral phos-
phorus or oral phosphorus and calcitriol. Maintenance
of good posture, positioning, and bracing in older chil-
dren are used to prevent deformities. After the disease
is controlled, deformities may have to be surgically cor-
rected as the child grows.
Paget Disease
Paget disease (i.e., osteitis deformans) is the second
most common bone disease after osteoporosis.
3,4,32,33
The disease, which has been described as a “collage
of matrix madness,” is characterized by focal areas of
excessive osteoclast-mediated bone reabsorption pre-
ceding disorganized osteoblast-mediated bone repair.
Paget disease usually begins during mid-adulthood and
becomes progressively more common with increasing
age, affecting about 5% of women and 8% of men by
the eighth decade of life.
32
It is more common in people
of Northern European heritage and is rare in Africans,
people of the Indian subcontinent, and Asians.
32
Etiology and Pathogenesis
Although the pathogenesis of Paget disease remains
unclear, there is evidence of both genetic and environ-
mental influences. It has been reported that 15% of per-
sons with the disease have a positive family history
32
and
numerous studies have described extended family mem-
bers with the disease.
31
There is increasing evidence that
Paget disease and some related diseases are caused by
mutations in genes encoding proteins in the RANK sig-
naling pathways.
3,4
Other evidence presents a probable
association with a virus, possibly a paramyxovirus, sug-
gesting that a viral infection may serve as a trigger for
development of Paget disease in genetically predisposed
individuals.
4,32
The incidence and severity of Paget dis-
ease of bone have decreased in recent years, possibly as a
result of improved nutrition, reduced exposure to infec-
tions, and a more sedentary lifestyle, which has had the
effect of reducing mechanical loading of the skeleton.
32
Paget disease is a focal process with considerable
variation in its stage of development in separate skeletal
sites.
33
At the onset, the disease is marked by regions
of furious osteoclastic bone resorption, followed by a
period of hectic bone formation with increased numbers
of osteoblasts rapidly depositing bone in a chaotic fash-
ion such that the newly formed bone is of poor quality
and is disorganized rather than lamellar. The poor qual-
ity of bone accounts for the bowing and fractures that
occur in bones affected by the disease. The bone mar-
row adjacent to the bone-forming surface is replaced
by loose connective tissue that contains osteoprogeni-
tor cells and numerous blood vessels, which transport
blood to and from these metabolically active sites. The
lesions of Paget disease may be solitary or may occur
in multiple sites. They tend to localize to the bones of
the axial skeleton, including the skull, spine, and pelvis.
The proximal femur and tibia may be involved in more
widespread forms of the disease. Histologically, Paget
lesions show increased vascularity and bone marrow
fibrosis with intense cellular activity. Numerous osteo-
clasts, large active osteoblasts, and peritrabular fibrosis
are encountered. The rapid remodeling leads to disrup-
tion of bone architecture. The bone has a somewhat
mosaic-like pattern resembling pieces of jigsaw puzzle,
separated by prominent areas of density, called
cement
lines
4
(Fig. 44-4).
Clinical Features
The clinical manifestations of Paget disease are extremely
variable and depend on the extent and site of the dis-
ease (see Fig. 44-4). The disease is usually asymptomatic
and discovered as an incidental radiograph finding.
32
Skeletal expansion and distortion may be obvious if
the disease affects the skull, jaw, clavicle, or long bones
of the leg. Involvement of the skull causes headaches,
intermittent tinnitus, vertigo, and eventual hearing loss.
The vertebrae of the spine may enlarge, weaken, and
collapse, causing kyphosis of the thoracic spine and
FIGURE 44-3.
A child suffering from nutritional rickets. Note
the bowed legs, protruding abdomen, and enlarged left wrist.
(From the Centers for Disease Control and Prevention Public
Health Images Library. No. 2435.)
